RT info:eu-repo/semantics/article T1 A double safety lock tumor-specific device for suicide gene therapy in breast cancer A1 Piña Lancho, María Jesús A1 Girotti, Alessandra A1 Serrano, Sofía A1 Muñoz Martínez, Raquel A1 Rodríguez Cabello, José Carlos A1 Arias Vallejo, Francisco Javier K1 Elastin-like recombinamers K1 Recombinantes tipo elastina K1 Nanocarriers K1 Nanoportadores K1 Suicide gene therapy K1 Terapia génica suicida K1 Breast cancer K1 Cáncer de mama AB The complexity and continuous evolution of cancer make the design of novel strategies of treatment a constant challenge in biomedicine. Moreover, most of cancer treatments are still not tumor-specific and provoke high systemic toxicity. Herein we have developed a novel selective nanodevice to eliminate tumor cells while leaving healthy ones intact. To achieve this objective, a polyplex carrier, comprising an elastin like-recombinamer covalently conjugated to an aptamer and complexed with therapeutic DNA, was tested. This carrier forms a double-lock multifunctional device due to specific binding to a tumor cell marker and the selective expression of therapeutic DNA inside human breast-cancer cells. Due to the stability provided by ELRs, the homogeneous population of polyplexes obtained showed selective toxicity against cancer cells in in vitro and in vivo assay. Inhibition of tumor progression was detected early being very significant at the end point, with a dose-dependent reduction in tumor mass. Histological studies revealed a specific reduction in tumor parenchyma and in specific tumor cell markers. These results represent an important step toward the rational development of an efficient, safe and more specialized gene-delivery device for tumor therapy. PB Elsevier SN 0304-3835 YR 2020 FD 2020 LK http://uvadoc.uva.es/handle/10324/40378 UL http://uvadoc.uva.es/handle/10324/40378 LA eng NO Cancer Letters, 2020, vol. 470. p. 43-53 NO Producción Científica DS UVaDOC RD 26-abr-2024